Anupama Rao

Intravenous administration of80mg ofrecombinant tissue plasminogen activator (rt- PA,40,20,and20mg insuccessive hours) andstreptokinase (SK,1.5million units over1hr) was compared inadouble-blind, randomized trial in290patients withevolving acutemyocardial infarc- tion. Thesepatients entered thetrial within 7hroftheonsetofsymptomsandunderwent baseline coronaryarteriography before thrombolytic therapy was instituted. Ninety minutes after thestart of thrombolytic therapy, occluded infarct-related arteries hadopened in62%of113patients inthert-PA and31%of119patients intheSK group(p<.001). Twice asmany occluded infarct-related arteries opened after rt-PA compared withSKatthetimeofeachofsevenangiograms obtained during thefirst 90minafter commencing thrombolytic therapy. Regardless ofthetimefromonsetofsymptomsto treatment, more arteries wereopened after rt-PA thanSK.Thereduction incirculating fibrinogen and plasminogen andtheincrease incirculating fibrin split products at3and24hrweresignificantly less in patients treated withrt-PA thaninthose treated withSK(p<.001). Theoccurrenceofbleeding events, administration ofblood transfusions, andreocclusion oftheinfarct-related artery was comparable inthe twogroups.Thus, inpatients with acutemyocardial infarction, rt-PA elicited reperfusion intwice as many occluded infarct-related arteries ascompared withSKateachofsevenserial observations during thefirst 90minafter onsetoftreatment. Circulation 76,No.1,142-154, 1987.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.

INTRODUCTION: There are no randomized controlled trial data that evaluate mortality and hospitalization rates in cardiac resynchronization therapy (CRT) recipients based on left ventricular (LV) lead location. We analyzed the event-driven outcomes of mortality and hospitalization as well as functional outcomes including Functional Class, Quality-of-Life, and 6-minute walk distance in 1,520 patients enrolled in the COMPANION study of CRT versus optimal medical therapy. METHODS AND RESULTS: Over a mean follow-up after implantation of 16.2 months, patients randomized to CRT, regardless of lead location, experienced benefit compared with optimized pharmacologic therapy (OPT), with respect to all-cause mortality or heart failure hospitalization. All but a posterior location showed benefit with respect to the all-cause mortality or all-cause hospitalization outcome. Mortality benefit in CRT-D patients was indifferent to LV lead position. All functional outcomes including 6-minute walk distance, Quality-of-Life (QOL) and Functional Class improved with CRT, regardless of LV lead location. CONCLUSION: LV lead location was not a major determinant of multiple measures of response to CRT therapy in the COMPANION Trial. While acute data indicate that a left lateral LV lead location results in the most favorable hemodynamic response, these chronic data suggest that positioning an LV lead in an anterior rather than a lateral or posterior LV location has similar benefit.